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bioRxiv · 10.1101/2021.04.24.441228

A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

Harris, P.·Brasel, T.·Massey, C.·Herst, C.·Burkholz, S.·Lloyd, P.·Blankenberg, T.·Bey, T.·Carback, R.·Hodge, T.·Ciotlos, S.·Wang, L.·Comer, J. E.·Rubsamen, R. M.
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Abstract

BackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy. MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis. ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques. ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/441228v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@c0730aorg.highwire.dtl.DTLVardef@c0bff7org.highwire.dtl.DTLVardef@7b1ea6org.highwire.dtl.DTLVardef@11950a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Harris, P., Brasel, T., Massey, C., Herst, C., Burkholz, S., Lloyd, P., Blankenberg, T., Bey, T., Carback, R., Hodge, T., Ciotlos, S., Wang, L., Comer, J. E., Rubsamen, R. M.. 2021-04-26. A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques. https://doi.org/10.1101/2021.04.24.441228

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